Tumor necrosis factor monoclonal antibody prevents alterations in leukocyte populations during cardiopulmonary bypass

Abstract

Tumor necrosis factor-alpha (TNF-alpha) has been implicated as causing the systemic inflammatory response to cardiopulmonary bypass (CPB) that contributes to the postoperative sequelae of coagulopathy, increased capillary permeability, leukocytosis, fever, and multiple organ dysfunction. To define the role of TNF-alpha on leukocyte populations during CPB, pigs (n = 6) were pretreated with 20 mg TNF-alpha monoclonal murine antibody before normothermic CPB (2 hr) in a blinded prospective randomized study with saline used as a control (n = 6). The leukocyte response to CPB was measured at 10, 30, 60, and 120 min during CPB and at 60 and 120 min after CPB. Repeated measures analysis of variance was performed and the null hypothesis was discarded at the 5% level. The control group displayed the typical leukocyte profile associated with CPB: and initial leukopenia (36% reduction) followed by leukocytosis (11% increase, P = 0.0001). The initial leukopenia was due to a fall in both polymorphonuclear neutrophils (33% reduced, P < 0.05) and monocytes (37% reduced, P < 0.05). In the TNF-alpha monoclonal murine antibody group the total leukocyte profile did not change significantly from baseline, (8.7% reduction to a 16% increase, P = 0.24) nor were there significant changes in populations including neutrophils and lymphocytes. In the treatment group the initial reduction in monocytes was prevented and total circulating monocytes increased during bypass. The experimental data suggest that TNF-alpha may play an important role in the early alterations in leukocyte populations associated with CPB, and TNF-alpha monoclonal murine antibody pretreatment ameliorates the leukocyte response.